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All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

SU-F-BRD-06: Robust Dose Calculation in Intensity Modulated Proton Therapy

Purpose: Commissioning data for intensity modulated proton therapy (IMPT) must be post-processed by fits to ad-hoc functions to derive the dose calculation kernel parameters in a treatment planning system (TPS). Whether from experimental measurement or Monte Carlo simulation, the limited and noisy nature of such data makes this task very challenging. We present a method to improve the modeling of the lateral dose distribution of clinical energy proton beams in water to commission an in-house IMPT dose calculation engine. Methods: A linear sum of three Gaussian distribution functions was fitted to the lateral dose data in logarithmic scale. Starting values of fitting solutions were determined from the Generalized Highland Approximation. We exhaustively optimized the combinations of data weights with upper bounds of the fitting solutions to minimize confidence intervals of the fitting solutions while maintaining the coefficient of determination (R{sup 2}). Results: Across all energies, average confidence bounds improved 72.88% [Max: 88.28%, Min: 55.05%] for small angle coulomb scattering, 114.25% [409.13%, 66.72%,] for nuclear scattering, and 68.66% [141.09%, 33.27%] for large angle coulomb scattering, while the coefficients of determination of the fits (R{sup 2}) remained comparable. On average R {sup 2} only changed 0.18% and were very close to 1 (approx. 0.999). Wilcoxon signed rank tests comparing unweighted/unbounded fits with weighted/bounded fits averaged 0.0146 (Max: 0.177, Min: 7.05×10−{sup 7}) for small angle Coulomb, 0.0903 (0.945, 7.05×10−{sup 7}) for nuclear, and 0.254 (0.871, 1.86×10−{sup 6}) for large angle Coulomb scattering. This allows rejection of the null hypothesis for small angle Coulomb scattering at the 0.015 level and nuclear interaction at the 0.1 level. Conclusion: Optimal weights assigned to IMPT lateral dose data minimized fitting to stochastic noise in the tail region. Optimizing the upper bounds of fitting parameters improved the robustness of fitting solutions. Both led to a more physically meaningful dose calculation kernel for the TPS. NIH/NCI K25CA168984, Eagles Cancer Research Career Development, The Lawrence W. and Marilyn W. Matteson Fund for Cancer Research, Mayo ASU Seed Grant, and The Kemper Marley Foundation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

A novel approach to assess the treatment response using Gaussian random field in PET

Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robust approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (128{sup 2} pixels) with lesions of various diameters (2–6 mm), multiple tumor-to-background contrasts (3–10), and different changes in intensity (6.25%–30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response assessment utilizing local average method based on random field. The accuracy of the estimation was validated in terms of Euler distance and correlation coefficient. Results: It is shown that the performance of therapy response assessment is significantly improved by the introduction of variance with a higher area under the curve (97.3%) than SUVmean (91.4%) and SUVmax (82.0%). In addition, the FPR estimation serves as a good prediction for the specificity of the proposed method, consistent with simulation outcome with ∼1 correlation coefficient. Conclusions: In this work, the authors developed a method to evaluate therapy response from PET images, which were modeled as Gaussian random field. The digital phantom simulations demonstrated that the proposed method achieved a large reduction in statistical variability through incorporating knowledge of the variance of the original Gaussian random field. The proposed method has the potential to enable prediction of early treatment response and shows promise for application to clinical practice. In future work, the authors will report on the robustness of the estimation theory for application to clinical practice of therapy response evaluation, which pertains to binary discrimination tasks at a fixed location in the image such as detection of small and weak lesion.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

SU-F-J-80: Deformable Image Registration for Residual Organ Motion Estimation in Respiratory Gated Treatments with Scanned Carbon Ion Beams

Purpose: At the Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy) C-ions respiratory gated treatments of patients with abdominal tumours started in 2014. In these cases, the therapeutic dose is delivered around end-exhale. We propose the use of a respiratory motion model to evaluate residual tumour motion. Such a model requires motion fields obtained from deformable image registration (DIR) between 4DCT phases, estimating anatomical motion through interpolation. The aim of this work is to identify the optimal DIR technique to be integrated in the modeling pipeline. Methods: We used 4DCT datasets from 4 patients to test 4 DIR algorithms: Bspline, demons, log-domain and symmetric log domain diffeomorphic demons. We evaluate DIR performance in terms of registration accuracy (RMSE between registered images) and anatomical consistency of the motion field (Jacobian) when registering end-inhale to end-exhale. We subsequently employed the model to estimate the tumour trajectory within the ideal gating window. Results: Within the liver contour, the RMSE is in the range 31–46 HU for the best performing algorithm (Bspline) and 43–145 HU for the worst one (demons). The Jacobians featured zero negative voxels (which indicate singularities in the motion field) for the Bspline fields in 3 of 4 patients, whereas diffeomorphic demons fields showed a non-null number of negative voxels in every case. GTV motion in the gating window measured less than 7 mm for every patient, displaying a predominant superior-inferior (SI) component. Conclusion: The Bspline algorithm allows for acceptable DIR results in the abdominal region, exhibiting the property of anatomical consistency of the computed field. Computed trajectories are in agreement with clinical expectations (small and prevalent SI displacements), since patients lie wearing semi-rigid immobilizing masks. In future, the model could be used for retrospective estimation of organ motion during treatment, as guided by the breathing surrogate signal.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TH-AB-201-06: Examining the Influence of Humidity On Reference Ion Chamber Performance

Purpose: International dosimetry protocols require measurements made with a vented ionization chamber to be corrected for the influence of air density by using the standard temperature-pressure correction factor. The effect of humidity, on the other hand, is generally ignored with the provision that the relative humidity is between certain limits (15% to 80%). However, there is little experimental data in the published literature as to the true effect of humidity on modern reference-class ion chambers. This investigation used two different radiation beams – a Co-60 irradiator and a Sr-90 check source – to examine the effect of humidity on several versions of the standard Farmer-type ion chamber. Methods: An environmental cabinet controlled the humidity. For the Co-60 beam, the irradiation was external, whereas for the Sr-90 measurements, the source itself was placed within the cabinet. Extensive measurements were carried out to ensure that the experimental setup provided reproducible readings. Four chamber types were investigated: IBA FC65-G (×2), IBA FC65-P, PTW30013 & Exradin A19. The different wall materials provided potentially different mechanical responses (i.e., in terms of expansion/contraction) to the water content in the air. The relative humidity was varied between 8 % and 97 % and measurements were made with increasing and decreasing humidity to investigate possible hysteresis effects. Results: Measurements in Co-60 were consistent with the published data obtained with primary standard cavity chambers in ICRU Report 31. Ionization currents with Sr-90 showed no dependence with the relative humidity, within the measurement uncertainties. Very good repeatability of the ionization current was obtained over successive wet/dry cycles, no hysteresis was observed, and there was no dependence on chamber type. Conclusion: This null result is very encouraging as it indicates that humidity has no significant effect on these particular types of ionization chambers, consistent with recommendations in current megavoltage dosimetry protocols.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Climatic warming destabilizes forest ant communities

How will ecological communities change in response to climate warming? Direct effects of temperature and indirect cascading effects of species interactions are already altering the structure of local communities, but the dynamics of community change are still poorly understood. We explore the cumulative effects of warming on the dynamics and turnover of forest ant communities that were warmed as part of a 5-year climate manipulation experiment at two sites in eastern North America. At the community level, warming consistently increased occupancy of nests and decreased extinction and nest abandonment. This consistency was largely driven by strong responses of a subset of thermophilic species at each site. As colonies of thermophilic species persisted in nests for longer periods of time under warmer temperatures, turnover was diminished, and species interactions were likely altered. We found that dynamical (Lyapunov) community stability decreased with warming both within and between sites. These results refute null expectations of simple temperature-driven increases in the activity and movement of thermophilic ectotherms. The reduction in stability under warming contrasts with the findings of previous studies that suggest resilience of species interactions to experimental and natural warming. In the face of warmer, no-analog climates, communities of the future may become increasingly fragile and unstable.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

New Model for Electron Flow for Sulfate Reduction in Desulfovibrio alaskensis G20

To understand the energy conversion activities of the anaerobic sulfate-reducing bacteria, it is necessary to identify the components involved in electron flow. The importance of the abundant type I tetraheme cytochrome c3 (TpIc3) as an electron carrier during sulfate respiration was questioned by the previous isolation of a null mutation in the gene encoding TpIc3, cycA, in Desulfovibrio alaskensis G20. Whereas respiratory growth of the CycA mutant with lactate and sulfate was little affected, growth with pyruvate and sulfate was significantly impaired. We have explored the phenotype of the CycA mutant through physiological tests and transcriptomic and proteomic analyses. Data reported here show that electrons from pyruvate oxidation do not reach adenylyl sulfate reductase, the enzyme catalyzing the first redox reaction during sulfate reduction, in the absence of either CycA or the type I cytochrome c3:menaquinone oxidoreductase transmembrane complex, QrcABCD. In contrast to the wild type, the CycA and QrcA mutants did not grow with H2 or formate and sulfate as the electron acceptor. Transcriptomic and proteomic analyses of the CycA mutant showed that transcripts and enzymes for the pathway from pyruvate to succinate were strongly decreased in the CycA mutant regardless of the growth mode. Neither the CycA nor the QrcA mutant grew on fumarate alone, consistent with the omics results and a redox regulation of gene expression. We conclude that TpIc3 and the Qrc complex are D. alaskensis components essential for the transfer of electrons released in the periplasm to reach the cytoplasmic adenylyl sulfate reductase and present a model that may explain the CycA phenotype through confurcation of electrons.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2014

The highly conserved MraZ protein is a transcriptional regulator in Escherichia coli

The mraZ and mraW genes are highly conserved in bacteria, both in sequence and location at the head of the division and cell wall (dcw) gene cluster. Although MraZ has structural similarity to the AbrB transition state regulator and the MazE antitoxin, and MraW is known to methylate ribosomal RNA, mraZ and mraW null mutants have no detectable growth phenotype in any species tested to date, hampering progress in understanding their physiological role. Here we show that overproduction of Escherichia coli MraZ perturbs cell division and the cell envelope, is more lethal at high levels or in minimal growth medium, and that MraW antagonizes these effects. MraZGFP localizes to the nucleoid, suggesting that it binds DNA. Indeed, purified MraZ directly binds a region upstream from its own promoter containing three direct repeats to regulate its own expression and that of downstream cell division and cell wall genes. MraZ-LacZ fusions are repressed by excess MraZ but not when DNA binding by MraZ is inhibited. RNAseq analysis indicates that MraZ is a global transcriptional regulator with numerous targets in addition to dcw genes. One of these targets, mioC, is directly bound by MraZ in a region with three direct repeats.

antitoxin↗
DOE OSTI2016

Novel Structure and Unexpected RNA-Binding Ability of the C-Terminal Domain of Herpes Simplex Virus 1 Tegument Protein UL21

Proteins forming the tegument layers of herpesviral virions mediate many essential processes in the viral replication cycle, yet few have been characterized in detail. UL21 is one such multifunctional tegument protein and is conserved among alphaherpesviruses. While UL21 has been implicated in many processes in viral replication, ranging from nuclear egress to virion morphogenesis to cell-cell spread, its precise roles remain unclear. Here we report the 2.7-Å crystal structure of the C-terminal domain of herpes simplex virus 1 (HSV-1) UL21 (UL21C), which has a unique α-helical fold resembling a dragonfly. Analysis of evolutionary conservation patterns and surface electrostatics pinpointed four regions of potential functional importance on the surface of UL21C to be pursued by mutagenesis. In combination with the previously determined structure of the N-terminal domain of UL21, the structure of UL21C provides a 3-dimensional framework for targeted exploration of the multiple roles of UL21 in the replication and pathogenesis of alphaherpesviruses. Additionally, we describe an unanticipated ability of UL21 to bind RNA, which may hint at a yet unexplored function. IMPORTANCE Due to the limited genomic coding capacity of viruses, viral proteins are often multifunctional, which makes them attractive antiviral targets. Such multifunctionality, however, complicates their study, which often involves constructing and characterizing null mutant viruses. Systematic exploration of these multifunctional proteins requires detailed road maps in the form of 3-dimensional structures. In this work, we determined the crystal structure of the C-terminal domain of UL21, a multifunctional tegument protein that is conserved among alphaherpesviruses. Structural analysis pinpointed surface areas of potential functional importance that provide a starting point for mutagenesis. In addition, the unexpected RNA-binding ability of UL21 may expand its functional repertoire. The structure of UL21C and the observation of its RNA-binding ability are the latest additions to the navigational chart that can guide the exploration of the multiple functions of UL21.

Metrick, Claire M.↗
DOE OSTI2022

Functional Traits Resolve Mechanisms Governing the Assembly and Distribution of Nitrogen-Cycling Microbial Communities in the Global Ocean

Microorganisms drive much of the marine nitrogen (N) cycle, which jointly controls the primary production in the global ocean. However, our understanding of the microbial communities driving the global ocean N cycle remains fragmented. Focusing on “who is doing what, where, and how?”, this study draws a clear picture describing the global biogeography of marine N-cycling microbial communities by utilizing the Tara Oceans shotgun metagenomes. The marine N-cycling communities are highly variable taxonomically but relatively even at the functional trait level, showing clear functional redundancy properties. The functional traits and taxonomic groups are shaped by the same set of geo-environmental factors, among which, depth is the major factor impacting marine N-cycling communities, differentiating mesopelagic from epipelagic communities. Latitudinal diversity gradients and distance-decay relationships are observed for taxonomic groups, but rarely or weakly for functional traits. The composition of functional traits is strongly deterministic as revealed by null model analysis, while a higher degree of stochasticity is observed for taxonomic composition. Integrating multiple lines of evidence, in addition to drawing a biogeographic picture of marine N-cycling communities, this study also demonstrated an essential microbial ecological theory—determinism governs the assembly of microbial communities performing essential biogeochemical processes; the environment selects functional traits rather than taxonomic groups; functional redundancy underlies stochastic taxonomic community assembly.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

River sinuosity describes a continuum between randomness and ordered growth

River channels are among the most common landscape features on Earth. An essential characteristic of channels is sinuosity: their tendency to take a circuitous path, which is quantified as along-stream length divided by straight-line length. River sinuosity is interpreted as a characteristic that either forms randomly at channel inception or develops over time as meander bends migrate. Studies tend to assume the latter and thus have used river sinuosity as a proxy for both modern and ancient environmental factors including climate, tectonics, vegetation, and geologic structure. But no quantitative criterion for planform expression has distinguished between random, initial sinuosity and that developed by ordered growth through channel migration. This ambiguity calls into question the utility of river sinuosity for understanding Earth’s history. We propose a quantitative framework to reconcile these competing explanations for river sinuosity. Using a coupled analysis of modeled and natural channels, we show that while a majority of observed sinuosity is consistent with randomness and limited channel migration, rivers with sinuosity ≥1.5 likely formed their geometry through sustained, ordered growth due to channel migration. This criterion frames a null hypothesis for river sinuosity that can be applied to evaluate the significance of environmental interpretations in landscapes shaped by rivers. The quantitative link between sinuosity and channel migration further informs strategies for preservation and restoration of riparian habitat and guides predictions of fluvial deposits in the rock record and in remotely sensed environments from the seafloor to planetary surfaces.

58 GEOSCIENCES↗
DOE OSTI2016

Dynamics of anisotropic power-law f(R) cosmology

Modified theories of gravity have attracted much attention of the researchers in the recent years. In particular, the f(R) theory has been investigated extensively due to important f(R) gravity models in cosmological contexts. This paper is devoted to exploring an anisotropic universe in metric f(R) gravity. A locally rotationally symmetric Bianchi type I cosmological model is considered for this purpose. Exact solutions of modified field equations are obtained for a well-known f(R) gravity model. The energy conditions are also discussed for the model under consideration. The viability of the model is investigated via graphical analysis using the present-day values of cosmological parameters. The model satisfies null energy, weak energy, and dominant energy conditions for a particular range of the anisotropy parameter while the strong energy condition is violated, which shows that the anisotropic universe in f(R) gravity supports the crucial issue of accelerated expansion of the universe.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2017

Dark matter constraints from an observation of dSphs and the LMC with the Baikal NT200

We have analyzed the neutrino events recoded in the deep-water neutrino experiment NT200 in Lake Baikal in five years of observations toward dark dwarf spheroidal galaxies (dSphs) in the southern hemisphere and the Large Magellanic Cloud (LMC). This analysis completes the series of works based on NT200 data in the search for a dark matter annihilation signal in astrophysical objects. We have found no significant excess in the number of observed events relative to the expected background from atmospheric neutrinos in all tested directions, in 22 dSphs and the LMC. For a sample of five selected dwarf galaxies we have performed a joint analysis of the data by the maximum likelihood method. We have obtained a correspondence of the observational data to the null hypothesis about the presence of only background events and established 90% confidence-level upper limits for the annihilation cross sections of dark matter particles with a mass from 30 GeV to 10 TeV in several annihilation channels both in the joint analysis of the selected sample of galaxies and in the analysis toward the LMC. The strongest constraints at a level of 7 × 10{sup –21} cm{sup 3} s{sup –1} have been obtained for the direction toward the LMC in the channel of annihilation into a pair of neutrinos.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Spin observables in proton-deuteron scattering and T-invariance test

The total cross section for the interaction of transversely polarized protons p{sub p}{sup y} and deuterons that have a tensor polarization P{sub x}{sup z} provides a null-test signal of T-invariance violation under the condition of P invariance. The relevant experiment is planned by the PAX Collaboration at the COSY accelerator with protons accelerated to the energy of 135 MeV. A modified Glauber theory is used here to calculate the differential spin observables A{sub y}, C{sub y,y}, C{sub xz,y}, C{sub z,x}, and C{sub x,z} and the differential and total cross sections for proton-deuteron scattering in the case of T-even P-even proton-nucleon interactions. This makes it possible to estimate background conditions of the planned experiment.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2013

Delta-Gravity (Physics of Particles and Nuclei, v. 44(2))

We present a model of the gravitational field based on two symmetric tensors. The equations of motion of test particles are derived: Massive particles do not follow a geodesic but massless particles trajectories are null geodesics of an effective metric. Outside matter, the predictions of the model coincide exactly with General Relativity, so all classical tests are satisfied. In Cosmology, we get accelerated expansion without a cosmological constant. Additionally, we study the quantization of the model. The main result being that the Effective Action is finite and receives one loop corrections only.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2013

Cusped light-like Wilson loops in gauge theories

We propose and discuss a new approach to the analysis of the correlation functions which contain light-like Wilson lines or loops, the latter being cusped in addition. The objects of interest are therefore the light-like Wilson null-polygons, the soft factors of the parton distribution and fragmentation functions, high-energy scattering amplitudes in the eikonal approximation, gravitational Wilson lines, etc. Our method is based on a generalization of the universal quantum dynamical principle by J. Schwinger and allows one to take care of extra singularities emerging due to lightlike or semi-light-like cusps. We show that such Wilson loops obey a differential equation which connects the area variations and renormalization group behavior of those objects and discuss the possible relation between geometrical structure of the loop space and area evolution of the light-like cusped Wilson loops.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2016

Ultracold neutrons and the interaction of waves with moving matter

The present review is focused on the problem of interaction of neutron waves with moving matter. The validity of the 1/ v law for ultracold neutrons and the possibility to characterize the interaction of neutrons with matter using the effective potential were verified in the so-called null Fizeau experiments. A neutron wave in such experiments propagates through a flat sample that moves parallel to its edges. The observation of effects caused by this motion provides evidence that the concept of constant effective potential is not correct. The second part of the review deals with the prediction and the first observation of the accelerated matter effect (a change in the energy of neutrons in passing through a refractive sample that moves with an acceleration directed along or opposite the direction of neutron propagation). The characteristic features of this phenomenon in the case of birefringent material are considered. In conclusion, the problem of propagation of neutron waves in matter moving with giant acceleration is discussed.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2018

Search for Time-Invariance Violation in Proton–Deuteron Scattering

In the TRIC experiment, the invariance under T -inversion assuming P -parity conservation is tested in the scattering of protons with transverse polarization p{sub y}{sup p} on deuterons with tensor polarization P{sub xz}. Theoretical predictions for the corresponding null-test signal as a function of beam energy in the 100–1000 MeV range obtained in the framework of the Glauber theory with T -violating NN interaction potentials are reviewed.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2018

On Non-Relativistic 3D Spin-1 Theories

We describe non-relativistic limits of the 3D Proca and √(Proca) theories that yield spin-1 Schroedinger equations. Analogous results are found by generalized null reduction of the 4D Maxwell or complex self-dual Maxwell equations. We briefly discuss the extension to spin-2.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗